Institute of Orthopedic Diseases and Center for Joint Surgery and Sports Medicine, The First Affiliated Hospital , Jinan University , Guangzhou 510630 , P. R. China.
Department of Genetics , University of Cambridge , Cambridge CB2 3EH , United Kingdom.
ACS Appl Mater Interfaces. 2019 Apr 24;11(16):14608-14618. doi: 10.1021/acsami.9b01532. Epub 2019 Apr 15.
Continuous delivery of growth factors to the injury site is crucial to creating a favorable microenvironment for cartilage injury repair. In the present study, we fabricated a novel sustained-release scaffold, stromal-derived factor-1α (SDF-1α)/transforming growth factor-β1 (TGF-β1)-loaded silk fibroin-porous gelatin scaffold (GSTS). GSTS persistently releases SDF-1α and TGF-β1, which enhance cartilage repair by facilitating cell homing and chondrogenic differentiation. Scanning electron microscopy showed that GSTS is a porous microstructure and the protein release assay demonstrated the sustainable release of SDF-1α and TGF-β1 from GSTS. Bone marrow-derived mesenchymal stem cells (MSCs) maintain high in vitro cell activity and excellent cell distribution and phenotype after seeding into GSTS. Furthermore, MSCs acquired enhanced chondrogenic differentiation capability in the TGF-β1-loaded scaffolds (GSTS or GST: loading TGF-β1 only) and the conditioned medium from SDF-1α-loaded scaffolds (GSTS or GSS: loading SDF-1α only) effectively promoted MSCs migration. GSTS was transplanted into the osteochondral defects in the knee joint of rats, and it could promote cartilage regeneration and repair the cartilage defects at 12 weeks after transplantation. Our study shows that GSTS can facilitate in vitro MSCs homing, migration, chondrogenic differentiation and SDF-1α and TGF-β1 have a synergistic effect on the promotion of in vivo cartilage forming. This SDF-1α and TGF-β1 releasing GSTS have promising therapeutic potential in cartilage repair.
持续向损伤部位输送生长因子对于构建有利于软骨损伤修复的微环境至关重要。在本研究中,我们构建了一种新型的缓释支架,即基质细胞衍生因子-1α(SDF-1α)/转化生长因子-β1(TGF-β1)负载丝素蛋白-多孔明胶支架(GSTS)。GSTS 持续释放 SDF-1α和 TGF-β1,通过促进细胞归巢和软骨分化来增强软骨修复。扫描电子显微镜显示 GSTS 具有多孔微结构,蛋白释放实验表明 SDF-1α和 TGF-β1 可以从 GSTS 中持续释放。骨髓间充质干细胞(MSCs)在接种到 GSTS 后保持高体外细胞活性和优异的细胞分布和表型。此外,MSCs 在负载 TGF-β1 的支架(GSTS 或 GST:仅负载 TGF-β1)和负载 SDF-1α 的支架的条件培养基(GSTS 或 GSS:仅负载 SDF-1α)中获得了增强的软骨分化能力,这些条件培养基可有效促进 MSCs 的迁移。GSTS 被移植到大鼠膝关节的骨软骨缺损部位,可在移植后 12 周促进软骨再生和修复软骨缺陷。我们的研究表明,GSTS 可促进体外 MSCs 归巢、迁移、软骨分化,SDF-1α 和 TGF-β1 对促进体内软骨形成具有协同作用。这种 SDF-1α 和 TGF-β1 释放的 GSTS 在软骨修复方面具有广阔的治疗潜力。